Ovarian cancer is the most lethal of gynecological malignancies with a mortality rate of 60%. The five-year survival rates for the various clinical stages of the disease are as follows: Stage I>90%, Stage II=80%, Stage III=20% and Stage IV=10%; there is a significant drop in the survival rates at later stages of the disease. Standard-of-care treatment for advanced stages of the disease includes cytoreductive surgery followed by chemotherapy.
For most patients there is a low probability of surviving, since approximately 75% of all patients are diagnosed at stages III and IV of the disease, and poor prognosis is associated with late diagnosis of the disease at its advanced stages. Resistance to currently-available chemotherapeutic agents is another major problem. Although complete clinical response is achieved in 75% of patients after initial treatment, most will develop recurrent disease and require re-treatment. Unfortunately, the overwhelming majority will eventually develop chemoresistance and succumb to the disease.
Chemoresistance is a complex phenomenon that involves a change in the expression and biological activity of several genes and gene products. The genes or gene families that are expressed differently in responsive and non-responsive individuals can be used as molecular markers for predicting which patients might be resistant to a particular chemotherapeutic agent or combination thereof, as is typically used clinically. In addition, genes that are overexpressed in chemoresistant individuals can be targets for inhibition, which may decrease resistance of a cancer cell to a chemotherapeutic agent or agents.
As with ovarian cancer, the survival of patients with colorectal cancer is best when the disease is diagnosed early. If the cancer is detected early, the 5-year survival rate for colon cancer patients is approximately 90%; unfortunately, despite increased surveillance and preventative measures, only 37% of cancers are found at this early stage. When the cancer has spread regionally to involve other organs the survival rate drops to around 64% and it is drastically lowered (8%) after the cancer has metastasized (Cancer Facts and Figures 2002; American Cancer Society publication).
Thus, there is a need for identifying colon and ovarian cancers early in the course of the disease process, and a particular need for identifying cancers that are chemoresistant. More specifically, since it is understood in the art that the behavior of cancer cells, both regarding their tumorigenicity and their resistance to chemotherapeutic drugs is mediated by the expression of a not completely defined set of particular genes, there is a need in the art to identify genes and collections or sets of genes that serve as effective molecular markers for chemoresistance in ovarian cancer, as well as such genes or gene sets that provide clinically effective therapeutic targets for ovarian cancer and colon cancer.